Cellular Uptake and Intracellular Antioxidant Activity of Zein/Chitosan Nanoparticles Incorporated with Quercetin

Abstract

In this work, zein/chitosan nanoparticles (ZCPs-Q) were developed for encapsulating quercetin to overcome its lower water solubility and instability, and to concomitantly enhance its cellular uptake and intracellular antioxidant activity. This strategy enhanced quercetin solubility 753.6 and 9.95 times in water and PBS (7.4), respectively, and quercetin encapsulated in ZCPs remained stable after UV irradiation and heat treatment. ZCPs-Q could significantly attenuate AAPH induced erythrocyte hemolysis through the inhibition of ROS generation. It restored intracellular antioxidant enzyme (SOD and GSH-Px) activities to normal levels and inhibited intracellular malondialdehyde (MDA) formation. Simultaneously, ZCPs-Q showed a strong antioxidant activity in HepG2 cells with an EC₅₀ value of 31.18 μg/mL, which was lower than free quercetin's 41.02 μg/mL. ZCPs enhanced the uptake efficiency of quercetin in Caco-2 cells, which contributed to the improvement of cellular antioxidant activities (CAA) evaluated with the CAA assay and AAPH-induced erythrocyte hemolysis assay. The designed route is particularly suitable for the encapsulation of water-insoluble nutraceuticals and for enhancing cell uptake and CAA.

Keywords: CAA; cell uptake; erythrocyte hemolysis; quercetin; zein/chitosan nanoparticles (ZCPs).